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SIX TH INT ERNATIONAL TINNITUS RESEARCH I NI T IATIVE CONF ERENCE


Vagus Nerve Stimulation: New Potential for Tinnitus Relief


By Will Rosellini, J.D., Ph.D., Jordan Curnes, MBA, Navzer Engineer, M.D., Ph.D.


Recent neuroscience research has demonstrated that some patients experience tinnitus as a result of abnor- mal firing of neurons in different parts of the brain. Although tinnitus is often described as ringing in the ear, the problem is in the brain. When one neuron sends a signal to another neuron(s) in the brain, it is typically referred to as a ‘spike’. When we hear sound, cells in the brain’s auditory areas generate a large number of spikes in complex patterns. Normally, in the absence of sound, the brain has a low level of this spiking activity. In a tinnitus brain, the neurons get highly excitable. Hundreds of thousands of nearby neurons fire simultaneously in a region called the auditory cortex. This simultaneous firing of brain cells is referred to as synchrony, which is thought to be one of the mechanisms responsible for sounds perceived by tinnitus patients, such as tones and crickets.


Navzer Engineer, M.D., Ph.D., from MicroTransponder, Inc., a Dallas based medical device company, in col- laboration with the Kilgard Brain Plasticity Laboratory at The University of Texas at Dallas has developed a technique that is intended to treat the excitable tinnitus brain by decreas- ing the abnormal


synchronous firing of auditory neurons. The technique combines stimulation of a nerve in the neck called the vagus nerve, with listening to specific tones. Using this method, researchers were able to treat tinnitus in a rat model by adjusting excitable neurons back down to a normal level of activity.


One might ask the question, “How can a nerve in the neck cause changes in the brain?” The vagus nerve is unlike any other nerve in the body. It directly connects to the brain and sends important signals to tell the brain what to learn. For example, when someone is exposed to a stressful event, a hormone called epinephrine is released into the bloodstream, which


28 Tinnitus Today | Summer 2012


activates the vagus nerve. The vagus nerve then sends a signal to the brain to release the neurotransmitter norepinephrine in a region called the amygdala, which strengthens memory storage for the emotional feelings of that specific time. This is why people often vividly remember traumatic events in specific detail. The vagus nerve is sending a signal telling the brain what to learn and when to learn it.


The MicroTransponder team utilizes this natural response system by directly stimulating the vagus nerve at the same time as playing a sound to tell the brain to “pay attention” to that sound. This simultane- ous pairing of a specific tone with vagus nerve stimu- lation (VNS) is thought to strengthen auditory neurons representing that tone. By consistently pairing VNS with all other tones except the tinnitus tone, the other neuron groups expand and the tinnitus tone neu- rons shrink. Over time, the brain learns to ignore the tinnitus tone. Pairing several of these tones (except the tinnitus tone) helped subdue the abnormal hyperac- tivity and restored the auditory cortex activity back to normal in a rat model of tinnitus. These changes


persisted for several weeks after stopping the treat- ment in this study. This study was published last year in the highly regarded academic journal, “Nature.”


More recently, MicroTransponder performed a clinical trial to evaluate the safety and preliminary effectiveness of Paired VNS Tone Therapy in humans, using a prototype version of the company’s planned fully implantable Serenity System™


*. A 10 patient


pilot clinical trial was carried out at the University Hospital Antwerp in Belgium under the supervision of ATA Scientific Advisory Committee member Dirk De Ridder, M.D., Ph.D., and his team. The goal of the study was to evaluate safety and potential benefits of


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